【作者】 张艳；

【导师】 李伯耿； 吴林波；

【作者基本信息】 浙江大学 ， 化学工程与技术， 2006， 博士

【摘要】 以生物质为资源合成可生物降解高分子材料，是解决高分子材料产业发展中资源短缺和环境污染等问题的一条可行途径。为开辟从生物质资源合成可生物降解高分子材料的新方法和新路线，本文从来源于生物质资源的乙酰丙酸出发，首先合成出5-羟基乙酰丙酸(5-HLA)单体，然后通过熔融缩聚，首次合成出聚5-羟基乙酰丙酸(PHLA)及其与二元醇、乳酸的共聚物，得到了一系列基于5-HLA的新型可生物降解聚合物，对单体合成和熔融缩聚的规律、聚合机理、聚合物的结构、性能以及降解行为等进行了系统的研究。以乙酰丙酸为原料，通过溴化，得到中间产物5-溴乙酰丙酸甲酯；又经一步水解、乙醚连续萃取和重结晶，得到了5-羟基乙酰丙酸。优化了溴化反应温度、液溴滴加速率、反应介质用量等溴化反应条件；同时利用3-溴乙酰丙酸甲酯等溴化物的分子内重排和歧化反应，对溴化反应生成的副产物回收再利用，将5-溴乙酰丙酸甲酯的产率从文献值30％提高到45％。一步水解法与文献的二步法相比，操作时间短，产率大大增加。为了得到5-羟基乙酰丙酸的内酯化产物，进而通过开环聚合得到新型脂肪族聚酯，设计了以三氟化硼／乙醚为催化剂进行5-羟基乙酰丙酸的内酯化反应路线，结果却得到了二聚体1，6，9，13-四氧双螺[4．2．4．2]十四烷-2，10-二酮(又称阿尔泰内酯)，它是中药九节菖蒲的化学成分之一。采用气质联用、核磁、红外、元素分析和多晶／单晶X射线衍射等方法对所得二聚体的结构进行了表征，并讨论了有关的反应机理。阿尔泰内酯非常稳定，难以进行开环聚合。为此，进行了对5-HLA的直接熔融缩聚研究，首次合成出低分子量的聚5-羟基乙酰丙酸。考察了反应条件如催化剂种类、催化剂用量、反应时间、反应温度等对缩聚反应的影响，发现以氯化亚锡／对甲基苯磺酸为催化剂时所得缩聚产物的分子量较高，颜色较浅。较佳的反应条件为170℃、18 h、氯化亚锡／对甲基苯磺酸为催化剂、用量0.7％，所得PHLA的分子量为M_w=2550，M_n=1660。并采用红外、核磁氢谱、核磁碳谱、X射线衍射、示差扫描量热以及热重分析等方法对这种新型的脂肪族聚酯的分子结构和热性能进行了表征，发现PHLA中存在烯醇式结构，易在聚合物分子内和分子间形成氢键，导致该聚合物具有异常高的玻璃化温度(M_n=1600时，T_g=128℃)。根据5-羟基乙酰丙酸或聚(5-羟基乙酰丙酸)中存在烯醇式结构的特点，将5-HLA与乙二醇(EG)、1，3-丙二醇(PO)、1，4-丁二醇(BDO)等二元醇进行熔融共缩聚，利用羟基与羧基的酯化缩合反应和烯醇式羟基与醇羟基之间的醚化缩合反应，首次实现了5-HLA与二元醇的非线性共缩聚反应，得到了化学交联的可生物降解聚合物聚(5-羟基乙酰丙酸-二元醇)(PHLA-diols)。该反应简单、易行，5-HLA与二元醇经脱水后加入催化剂，即可很快地生成交联聚合物。考察了二元醇、反应温度、单体配比、催化剂用量等反应条件对非线性缩聚产物结构和性能的影响。反应温度与催化剂用量的提高均会促进交联反应的进行，反应产物的凝胶含量增加；改变单体配比可在很宽的范围内调节反应产物的凝胶含量和T_g，改变二元醇的种类也可实现T_g的调节。在5-HLA／BDO体系中，发现在5-HLA／BDO的摩尔比为95／5～20／80的范围内均可以得到具有交联结构的共聚物PHLA-BDO，当5-HLA／BDO的摩尔比为40／60～80／20时，PHLA-BDO的凝胶含量可达90％以上。这些交联产物的玻璃化温度在-35.6℃～65.1℃范围内变化。因而5-羟基乙酰丙酸与二元醇共缩聚既可得到柔性的交联弹性体材料，又可得到刚性的半交联聚合物。但这些刚性的半交联聚合物经溶剂抽提后，玻璃化温度下降，也变为弹性体。这种玻璃化温度在抽提前后的变化可归结为交联点的形成破坏了分子内或分子间原有的氢键所致。红外表征结果表明聚合物链结构中存在酯键、烯醚键、双键，基本证实了推测的反应机理。此外，根据PHLA分子量低而玻璃化温度高、而聚乳酸分子量高而玻璃化温度低的特点，对5-HLA和乳酸的共缩聚反应进行了探索，以提高PHLA的分子量和聚乳酸的玻璃化温度。考察了单体配比、反应温度以及反应时间等条件对共缩聚反应的影响以及共聚物PHLA-LLA和PHLA-DLLA的结构和性能的变化规律。发现引入少量的L-乳酸(LLA)或DL-乳酸(DLLA)与5-HLA共聚，对提高聚合物分子量并无明显效果。引入少量5-HLA与L-乳酸共缩聚，可提高聚L-乳酸的玻璃化温度，而对于5-HLA与DL-乳酸的共聚物PHLA-DLLA，只有在5-羟基乙酰丙酸的共聚比例较高时，才能使其玻璃化温度有所提高。研究了PHLA、PHLA-BDO、PHLA-LLA、PHLA-DLLA的水解降解行为。由于存在脂肪族酯键，这些聚合物均能发生水解降解。与传统的脂肪族聚酯在降解的初始阶段不失重的规律不同，这些聚合物由于分子量较低，均从降解一开始就持续、平稳地失重。PHLA在37℃下在水中降解4周失重达50％，在PBS缓冲溶液中降解更快。PHLA-BDO由于化学交联网络结构的存在，降解失重速度比PHLA慢，样品降解6周后，重量损失30％左右。5-HLA与乳酸的共聚物随组成的不同，降解速率有较大的差别；结晶性的PHLA-LLA的降解速度比无定形的PHLA-DLLA要慢。更多还原

【Abstract】 Synthesizing biodegradable polymers such as polylactic acid from renewable biomass resource is one feasible way to solve the problems of environment pollution and resource shortage in current polymer industries. In this work, novel biodegradable polymers have been synthesized from biomass via a new synthetic route. In brief, 5-hydroxylavulinic acid （5-HLA）, an apparent hydroxyl acid monomer, was first synthesized from levulinic acid （LA）, a platform chemical derived from biomass resources; then, novel aliphatic polyesters including poly（5-hydroxylevulinic acid） （PHLA）, poly（5- hydroxylevulinic acid -co- diol）s （PHLA-DO）, poly（5-hydroxylevulinic acid -co- lactic acid）s （PHLA-LA） were synthezied via melt polycondensation of 5-HLA or co-polycondensation of 5-HLA with diols or lactic acids. The monomer synthesis, the polycondensation and copolycondensation reactions, the polymerization mechanism, the structures and properties and in vitro degradation behaviors of the resulting polymers and copolymers were studied systemically.In the synthesis of 5-HLA, LA was first brominated using liquid bromine （Br₂） to give an intermediate product methyl 5-bromolevulinate （5-MBL）, which was then hydrolyzed in one step to produce 5-HLA. After extraction of the hydrolysis product with diethyl ether and then recrystallization of the extract in chloroform, pure 5-HLA crystal was obtained with a yield of 28% （based on LA）. In the bromization reaction of LA, the reaction conditions such as reaction temperature, drop rate of Br₂ and reaction medium were optimized. Methyl 3-bromolevulinate （3-MBL） in the side product was partially converted to methyl 5-bromolevulinate （5-MBL） through a rearrangement reaction, thus the side product was partially reused and the yield of 5-MBL was enhanced from an ever reported value of 30% to 45%. The one-step hydrolysis of 5-MBL resulted in shorter reaction time and higher yield and is thus better than the two-step hydrolysis reported in literature.In an attempt to synthesize a lactone monomer form 5-HLA using BF₃·OEt₂ as catalyst, 1,6,9,13-tetraoxadispiro [4.2.4.2] tetradecane-2,10-dione （or altaicadispirolactone, ADPL）, a dimer of the 5-HLA, rather than the expected γ-keto-δ-valerolactone （KVL） was synthesized. ADPL is one of the chemical components of Anemone altaica C.A.May, a traditional Chinese medicinal herb. Structure of the dimer was characterized by GC-MS, ¹H-NMR, ¹³C-NMR, FT-IR, element analysis and polycrystal/single crystal XRD, respectively. Two plausible mechanisms for the cyclolactonization reaction were presented. However, this compound is too steady to be polymerized in ring-opening manner.Then, the melt polycondensation of 5-HLA was studied and low molecular weight poly(5-hydroxylevulinic acid （PHLA） was synthesized for the first time. The effects of reaction conditions such as catalyst type and amount, reaction time and reaction temperature on the polycondensation were examined. It was found that catalysts including Sn, SnO, SnCl₂·2H₂O and Sn（Oct）₂ exhibited catalytic activity for the polycondensation reaction, among which SnCl₂·2H₂O was the most effective one when it was used together with p-toluenesulfonic acid （TSA）. PHLA with M_W of about 2550 was synthesized in the presence of SnCl₂·2H₂O/TSA at 170℃ and under reduced pressure for 18 hours. The microstructure and thermal properties of PHLA were characterized with FTIR, ¹H-NMR, ¹³C-NMR, DSC and TGA. It was found that PHLA possesses unexpected high glass transition temperature （M_n = 1600, T_g, 128 ℃）. This is very different from ordinary aliphatic polyesters which usually have T_gs lower than 60℃. The high T_g is attributed to the formation of intra- and intermolecular hydrogen bonds because of existence of a characteristic keto-enol tautomerizm equilibrium in the polymer structure.Because of the existence the enol structure of 5-HLA, it is no longer merely a bifunctional hydroxyl acid monomer, but a trifunctional monomer. To utilize the enol hydroxyl of 5-HLA or PHLA, 5-HLA or oligomer of 5-HLA was copolycondensed with diol monomers such as butanediol （BDO）, 1,3-propanediol （PDO） and ethylene glycol （EG）. Crosslinked polymers were synthesized for the first time from these apparent 2-2 functional monomer systems via the esterification of the hydroxyl withthe carboxyl and the etherification of enol hydroxyl with the alcohol hydroxyl. Briefly, in a preferable synthesis route, 5-HLA was first dehydrated together with BDO under vacuum, and then a catalyst was added into the resulting prepolymer and the reaction was continued at atmospheric pressure, as a result, an crosslinked polymer was produced in short time. It is no longer soluble but swellable in tetrahydrofuran （THF, a good solvent for PHLA）. The change of gel content was tracked with time under various reaction conditions: diols, monomer ratios, reaction temperature and catalyst amount. The crosslinking reaction was accelerated with increasing temperature or catalyst concentration or using longer diol. The gel content and T_g of the copolymer could be manipulated by changing the monomer feed ratio. The length of the diol also affects the T_g. For the 5-HLA/BDO system, crosslinked polymers PHLA-BDO were produced within a 5-HLA/BDO molar ratio range from 95/5 to 20/80, and gel contents higher than 90% were reached in a 5-HLA/BDO molar ratio range from 40/60 to 80/20. The T_gs range from -35.6℃ to 65.1℃. Therefore, both soft crosslinked elastomers and rigid semi-crosslinked polymers could be obtained. But the rigid semi-crosslinked polymers changed to soft elastomers with decreased T_gs after extraction with THF. The decrease of T_g of the crosslinked polymer （compared with PHLA） may be attributed to the destroy of the hydrogen bonds because of the formation of the crosslinking point. The FT-IR spectrum of crosslinked PHLA-BDO validates the existence of ester bond, vinyl ether and double bond in the chain structure. This demonstrates the crosslinking mechanism suggested.As an attempt to increase the molecular weight of PHLA and T_g of poly（L-lactic acid） （PLLA） and poly（D,L-lactic acid） （PDLLA）, the copolycondensation of 5-HLA with L-lactic acid （LLA） and D,L-lactic acid （DLLA） was carried out respectively. The effects of the reaction conditions including monomer feed ratios, reaction temperature, catalyst amount and reaction time were investigated, and the structure and thermal properties of the resulting copolymer were studied. But in the copolycondensation with high 5-HLA/LLA or 5-HLA/DLLA ratio, the molecular weight of PHLA-LLA and PHLA-DLLA were not increased as compared with PHLA homopolymer. Obvious increase in molecular weight was only observed when thecontent of L-lactic acid or DL-lactic acid was higher than 90%. In copolycondensation with low 5-HLA/LLA ratio, addition of small amount of 5-HLA resulted in an obvious increase of T_g of the PHLA-LLA copolymer as compared with the PLLA homopolymer with same molecular weight. But it was not the case for PHLA-DLLA. Only when the content of 5-HLA is high enough, the T_g of PHLA-DLLA could be raised.The in vitro degradation behaviors of PHLA, PHLA-BDO, PHLA-LLA and PHLA-DLLA were examined at 37℃. It was found that PHLA degraded more rapidly in phosphate buffer saline （PBS） than in deionized water, but the sample degraded in PBS was no longer soluble in THF. Therefore, most of the degradation was performed in deionized water. Because of the hydrolytically sensitive aliphatic ester bonds in the structures of these polymers, they degraded readily in water. Weight loss appeared from the beginning of the degradation process possibly because of the lower molecular weight or existence of sol in the crosslinked samples. The weight loss of PHLA reached 40% after 4 weeks. But PHLA-BDO degraded more slowly because of crosslink. Its weight loss only reached 30% after 6 weeks. The degradation rate of PHLA-LLA and PHLA-DLLA was different according to the type of lactic acid and monomer ratios. Crystalline PHLA-LLA degraded more slowly than amphorous PHLA-DLLA.更多还原